Scientific Reports
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2025
·Vol. 15
·期 1
·1-11
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IF 3.9
Hu Lili,Wu Na,Wang Jue,Cai Donghui
The anti-inflammatory effect of phellodendrine (PHE), derived from Phellodendri Chinensis Cortex, has been verified in previous studies. Major depressive disorder (MDD) is associated with immune dysregulation and inflammatory processes. This study aimed to explore the therapeutic effects of PHE on MDD through network pharmacology and experimental validation. Multiple databases were used to predict the targets of PHE and MDD. The intersection targets between PHE and MDD were obtained to identify as targets for PHE against MDD, followed by protein–protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Molecular docking was applied to further confirm the anti-MDD effects of PHE. The mitochondrial DNA (mtDNA) copy number, inflammatory cytokines and pathway-related mRNA expressions in PC12 cell were determined via quantitative PCR (qPCR) and enzyme-linked immunosorbent assay to verify our finding. Thirty-eight intersection targets were obtained between PHE and MDD. PHE exerted an anti-MDD effect by regulating SLC6A4, SLC6A3, SLC6A2, MAOA and other targets through serotonergic synapse, salivary secretion, dopaminergic synapse, and cAMP signalling pathway. In vitro, PHE induced an increment in mtDNA copy number compared with the CORT group. PHE affected the levels of IL6 and IL1β with different concentrations. The mRNA levels of CHRM1, HTR1A and key targets of the PI3K/Akt signalling pathway were also influenced. Our research reveals novel mechanisms underlying the anti-MDD effects of PHE through network pharmacology and experiments, which provides a new direction for the development of antidepressants.
研究领域:
药理学
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神经科学
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DOI
PubMed
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2021
·Vol. 35
·期 18
·e9157
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IF 2.419
Feng-Xiang Zhang,Yu-Lin-Lan Yuan,Shuang-Shuang Cui,Min Li,Rui-Man Li
Rationale Characterizing the functional mechanism of quality control marker (Q-marker) was of great importance in revealing the primary pharmacological mechanism of herbs or the other complex system, and drug-related metabolites always contribute to the pharmacological functions. Cortex Phellodendri was used as a core herb in the treatment of diabetes mellitus (DM). As a Q-marker of Cortex Phellodendri, the role of phellodendrine in DM was still unclear. Thus, the characterization of phellodendrine-related metabolites in vivo and the subsequent induced functional mechanism exerted great importance in elucidating the anti-DM mechanism of Cortex Phellodendri. Methods An ultra-high-performance liquid chromatography-coupled time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method was developed to profile metabolites of phellodendrine in rats. The potential pharmacological mechanism against DM was predicted by network pharmacology. Results A total of 19 phellodendrine-related metabolites were screened out in rats for the first time. Among them, M4 , M5 , M9 , and M12 were regarded as the primary metabolites. Meanwhile, phase I metabolic reactions of hydroxylation, demethylation, and isomerization and phase II reactions of glucuronidation and sulfation occurred to phellodendrine; glucuronidation and hydroxylation were the two main metabolic reactions. Moreover, the potential targets of phellodendrine and three main metabolites ( M4 , M5 , and M12 ) were predicted by a network pharmacological method, and they mainly shared 52 targets, including PDE5A, CHRNA3, SIGMAR1, F3, ESR1, DRD1, DRD2, DRD3, and DRD4. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that calcium signaling pathway, cGMP-PKG signaling pathway, and cAMP signaling pathway were regarded as the core mechanism of phellodendrine to treat DM. Conclusion The metabolic feature of phellodendrine in vivo was revealed for the first time, and its anti-DM mechanism information for further pharmacological validations was also supplied. It also gave a direction to further elucidation of pharmacological mechanism of Cortex Phellodendri in treating DM.
研究领域:
药理学
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代谢组学
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DOI
高影响因子
IMMUNOBIOLOGY
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2025
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IF 2.3
Yu-yao Qin,Zi-yi Qin,Tao Liang,Dong-er Qin,Sheng-yi Hua,Ming-hui Tan,Shun Guo,Fan Yang,Le Shi,Yun Yu,Guang-ji Zhang
Background Phellodendrine, a primary bioactive constituent of Phellodendron chinense Schneid (PCS), is crucial in its pharmacological profile. Phellodendrine exhibits potent anti-nephritic properties and demonstrates a marked inhibitory effect on the cellular immune response. However, the effects of phellodendrine on proteoglycan depletion and cartilage degeneration in gouty arthritis remain insufficiently understood. Therefore, the objective of this study is to elucidate the therapeutic potential and underlying mechanisms of phellodendrine chloride (PC) in the treatment of gouty arthritis. Methods A monosodium urate (MSU)-induced arthritis model in rats, along with a peritonitis model in mice, was developed, in combination with a chondrocyte model. Neutrophil proportions were quantified using flow cytometry. The expression levels of MMP-3, STAT3, and phosphorylated STAT3 (p-STAT3) in chondrocytes were determined by Western blot analysis. Proteoglycan levels in chondrocytes were assessed using toluidine blue staining and quantitative reverse transcription PCR (qRT-PCR). Joint swelling rates were monitored at 0–24 h in rats, and histopathological changes in joint tissues were subsequently analyzed. Results Phellodendrine chloride mitigated the rise in neutrophil proportions within MSU-induced peritoneal lavage fluid in mice and decreased inflammatory cell infiltration in rat ankle tissues. Treatment with phellodendrine chloride led to a downregulation of MMP-3 protein levels and inhibited IL-1β-induced proteoglycan degradation in chondrocytes. Additionally, results from experiments combining IL-1β with AG490 or IL-6 demonstrated that phellodendrine chloride attenuated IL-1β-induced MMP-3 expression and proteoglycan degradation. Conclusion Our findings suggest that phellodendrine chloride mitigates gouty arthritis (GA) by modulating the IL-6/STAT3 signaling pathway.
研究领域:
药理学
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免疫学
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风湿病学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2024
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IF 4.5
Xueyu Pu,Yuanyuan Wang,Xi Wang,Xiaoqing Sang,Miaomiao Jiang,DaWei Qi,Xin Zhao,Rong Chen,Jianwei Li,Xiang Liu,Zhidong Liu,Jian Yang
Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen’s cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen’s cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.
研究领域:
药学
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纳米技术
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微生物学
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药物递送系统
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抗菌治疗
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DOI
PubMed
高影响因子
Separation Science Plus
·
2022
·Vol. 5
·期 6
·237-246
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IF 0
Min Lu,Hao Zhang,Shi-Jun Yin,Hui Jiang,Xu Wang,Feng-Qing Yang
In this study, the poly (sodium 4-styrenesulfonate)-mediated calcium carbonate magnetic microspheres were prepared by a simple spontaneous biomimetic mineralization method to immobilize kallikrein. The immobilized kallikrein can be easily separated from the reaction mixture by an external magnet. The structural properties of the materials were studied by several characterization techniques. Subsequently, the immobilized kallikrein enzyme activity and stability were studied. Moreover, the inhibitory potency of ten natural compounds on kallikrein was evaluated by combining with capillary electrophoresis analysis. The immobilized kallikrein exhibited optimum pH and temperature at 7.5 and 75°C, respectively. After seven successive cycles, the immobilized kallikrein retained 82% of its initial activity. Furthermore, the Michaelis–Menten constant ( K m ) and the half-maximal inhibitory concentration (IC 50 ) of serine protease inhibitor on the immobilized kallikrein were determined to be 3.30 mM and 67.04 μM, respectively. In addition, berberine, evodine, coptisine, and jatrorrhizine among the ten natural compounds showed good inhibitory activity on the immobilized kallikrein, and their % of inhibition were (43.1 ± 1.7), (34.4 ± 1.9), (38.0 ± 1.7), and (28.5 ± 1.0)%, respectively. These results indicate that the biomimetic mineralization synthetic magnetic microsphere is an efficient method for kallikrein immobilization.
研究领域:
材料科学
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生物化学
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酶工程
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药学
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DOI
Biomolecules
·
2026
·Vol. 16
·期 8
·1092
·
IF 5.6
Yufeng Xie,Ziyi Zhou,Xuqianzi Wu,Jiayin Teng,Xiaorun Zhang,Yue Sun,Lixin Chen,Lijian Ding,Wei Yuan
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Current treatments, including anti-inflammatory drugs and biologics, often have limited efficacy and significant side effects, highlighting the need for novel therapeutic approaches. Phellodendrine (PHE) is a characteristic ingredient ofPhellodendri chinensis, yet its effects and mechanisms on IBD remain elusive. The present study evaluated the potential of PHE for preventing dextran sulfate sodium-induced IBD in zebrafish. PHE effectively reduced inflammatory cell infiltration and modulated polarized macrophages. The qPCR results further confirmed the down-regulation of pro-inflammatory genes and up-regulation of anti-inflammatory factors. Consequently, PHE promoted the resolution of IBD inflammation. PHE also restored intestinal barrier integrity by enhancing MUC2 expression, increasing goblet cell counts, and reducing intestinal permeability of both chemical and physical barriers. In addition, PHE was associated with alterations in the gut microbiome, including a reduction in potentially pathogenic microbes and an increase in beneficial microbial populations. PHE also alleviated oxidative stress. Network pharmacology suggested the potential involvement of the IL-17 signaling pathway, the lipid and atherosclerosis pathway, and the TNF signaling pathway in the preventive effects of PHE against intestinal inflammation in the zebrafish model. In vivo gene expression analysis suggested that JUN, PTGS2, IL1B, DRD2, CALM1, and HSP90AA1 may serve as putative targets of PHE. Collectively, our results indicate that PHE demonstrates potential anti-inflammatory and barrier-protective activities in a zebrafish model of intestinal inflammation. The pharmacological mechanisms by which PHE restores intestinal barriers (microbial, chemical, physical, and immune barriers) include resolving inflammation, decreasing ROS production, and enhancing lipid accumulation in the lumen overlying the intestinal mucus barrier. This study provides novel insights into the preventive effects of PHE against intestinal inflammation in a zebrafish model, suggesting its potential as a candidate for further investigation.
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高影响因子
JOURNAL OF PLANT PHYSIOLOGY
·
2026
·
IF 4.8
Mengyuan Cui,Xu Huang,Chenxu Zhao,Surya Kant,Shanshan Yang,Wenxuan Zhu,Xiaorong Fan,Shubin Sun,Guohua Xu,Xiaowen Wang
Minimizing the accumulation of polycyclic aromatic hydrocarbons (PAHs) in crops is crucial for human health. While OsNRT2.3b overexpression reduced phenanthrene (Phe) in rice, the underlying mechanisms and its response to complex conditions remained unclear. This study first confirmed a negative correlation between OsNRT2.3b expression and Phe utilizing 16 varieties. Further, to investigate whether the pH-sensing site H167 of OsNRT2.3b is the key, the wild-type (WT), OsNRT2.3b -overexpression (Ox), and H167-mutated OsNRT2.3b overexpression (H167R) were employed to expose to Phe under different nitrogen (N) and pH. Individual N and pH experiments demonstrated that H167 played a decisive role in suppressing Phe, with Phe in H167R being significantly higher than Ox. Moreover, both -N compared to + N, and pH 4.0 compared to 7.0, increased Phe while simultaneously enhancing H167-mediated regulation. Phe in Ox was significantly lower than H167R by 24.6% (-N) and 22.3% (pH 4.0). Combined pH and N treatments revealed that H167 was most effective under acidic and N-deficient conditions. Under hydroponic pH 4.0 & -N and pot soil pH 5.4 & LN, Phe in the roots of Ox were 19.7% and 17.3% lower than H167R. Effect size analysis indicated that an acidic environment exerted a stronger effect on H167-mediated Phe reduction than N under the conditions tested. Notably, in grains, the pH-specific mediation by H167 decreased Phe by 16.6% under acidic and N-deficient soil. This study provides a basis for mitigating Phe accumulation and associated PAH-related risks in rice through molecular strategies and soil pH and N management.
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高影响因子
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